Effects of AT1 and AT2 angiotensin receptor antagonists in angiotensin II-infused rats.
Angiotensin II (Ang II) appears to exert its contractile and growth-promoting effects through the AT1 receptor subtype, whereas the AT2 subtype may have growth-inhibitory and proapoptotic properties. Recently, some data have challenged this emerging concept. To clarify the role of AT1 and AT2 receptors, we treated Wistar rats that were infused with Ang II (120 ng/kg/min subcutaneously by osmotic minipump), with the AT1 antagonist losartan (10 mg/kg/d in the drinking water) and the AT2 antagonist PD123319 (30 mg/kg/d subcutaneously by osmotic minipump) for 21 days. At the end of the study, tail-cuff systolic blood pressure was 106+/-2.8 mm Hg in untreated rats and 108+/-2.0 mm Hg in rats infused with Ang II that received losartan, whereas it rose to 158+/-4.9 mm Hg in Ang II-infused rats and 158+/-3.0 mm Hg in rats infused with Ang II rats and PD123319 (the two latter groups P<.01 versus the two other groups). Heart weight, and aorta cross-section/body weight ratio were higher in Ang II-infused rats than in controls and were significantly reduced in Ang II-infused rats that received losartan (P<.05). Wire-myograph-mounted coronary, renal, mesenteric, and femoral small arteries from Ang II-infused rats and Ang II-infused rats receiving PD123319 had a greater media, media cross-section, and media/lumen ratio than vessels from untreated or Ang II-infused rats treated with losartan. These results support the concept that in Wistar normotensive rats infused for 3 weeks with angiotensin II, growth in the heart, aorta, and coronary, renal, mesenteric, and femoral small arteries is mediated by the AT1 receptor; the results show little evidence of a role of AT2 receptors in mediating angiotensin II effects in this experimental paradigm.
Li
J S
JS
MRC Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montréal, University of Montréal, Québec, Canada.
Touyz
R M
RM
Schiffrin
E L
EL
D000284:Administration, Oral; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001013:Aorta, Thoracic / Q000033:anatomy & histology / Q000187:drug effects; D001158:Arteries / Q000033:anatomy & histology / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D003331:Coronary Vessels / Q000033:anatomy & histology / Q000187:drug effects; D005263:Femoral Artery / Q000033:anatomy & histology / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007263:Infusions, Parenteral; D007668:Kidney / Q000098:blood supply; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C073402:PD 123319; D019808:Losartan